Alvimopan, for postoperative ileus following bowel resection: a pooled analysis of phase III studies

Abstract

Objective: To obtain further analysis regarding specific outcomes and alvimopan doses in bowel resection (BR) patients.

Summary background data: Although postoperative ileus (POI) is common after BR, there is currently no recognized treatment or prevention available. Alvimopan, a novel, peripherally active mu-opioid receptor antagonist, accelerated GI recovery after BR or hysterectomy in 3 phase III trials.

Methods: A pooled retrospective subset analysis of BR patients in alvimopan phase III trials was performed. Randomized BR patients received alvimopan 6 mg (n = 397), 12 mg (n = 413), or placebo (n = 402) >or=2 hours before surgery and twice daily until hospital discharge for <or=7 days. The primary endpoint of each trial was time to recovery of GI function. Hospital discharge order (DCO) written, readmission, and morbidities were also assessed. Cox proportional hazard models were used to analyze treatment effects on time-to-event endpoints.

Results: Alvimopan (6 or 12 mg) significantly accelerated GI recovery (GI-3; hazard ratio = 1.28 and 1.38, respectively; P <or= 0.001 for both). Alvimopan significantly accelerated time to DCO written by 16 hours for 6 mg and 18 hours for 12 mg (P < 0.001 for both) from a mean of 147 hours for placebo. Alvimopan-treated patients had reduced postoperative morbidity compared with placebo, and incidence of prolonged hospital stay or readmission was significantly reduced (P < 0.001). Tolerability profiles were similar among groups.

Conclusions: Alvimopan significantly accelerated GI recovery in BR patients. A 12-mg dose provided more consistent benefits across both sexes and all ages. Postoperative morbidity rates, prolonged hospital stay, and rates of hospital readmission were significantly reduced. Alvimopan reduces the consequences of POI after BR.

FIGURE 1. Supplemental figure. Consort diagram. This schematic illustrates the study design for patient randomization and treatment and patient disposition. BR, bowel resection; MITT, modified intent to treat; AE, adverse event; WC, withdrew consent.

FIGURE 2. Hazard ratios and 95% CIs for time to recovery of GI function endpoints (MITT population). CI, confidence interval; GI, gastrointestinal; MITT, modified intent to treat; GI-3, recovery of bowel movement, passage of flatus, and toleration of solid food; GI-2, recovery of bowel movement and toleration of solid food; HD, hospital discharge based on GI recovery, as determined by the investigator; DCO, discharge order written.

FIGURE 3. Postoperative morbidity for bowel resection patients (safety population). NGT, nasogastric tube; POI, postoperative ileus; SAE, serious adverse event; EPSBO, early postoperative bowel obstruction.